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Cytidine 5'-monophosphate (CMP)-induced structural changes in a multifunctional sialyltransferase from Pasteurella multocida.

Sialyltransferases catalyze reactions that transfer a sialic acid from CMP-sialic acid to an acceptor (a structure terminated with galactose, N-acetylgalactosamine, or sialic acid). They are key enzymes that catalyze the synthesis of sialic acid-containing oligosaccharides, polysaccharides, and glycoconjugates that play pivotal roles in many critical physiological and pathological processes. The structures of a truncated multifunctional Pasteurella multocida sialyltransferase (Delta24PmST1), in the absence and presence of CMP, have been determined by X-ray crystallography at 1.65 and 2.0 A resolutions, respectively. The Delta24PmST1 exists as a monomer in solution and in crystals. Different from the reported crystal structure of a bifunctional sialyltransferase CstII that has only one Rossmann domain, the overall structure of the Delta24PmST1 consists of two separate Rossmann nucleotide-binding domains. The Delta24PmST1 structure, thus, represents the first sialyltransferase structure that belongs to the glycosyltransferase-B (GT-B) structural group. Unlike all other known GT-B structures, however, there is no C-terminal extension that interacts with the N-terminal domain in the Delta24PmST1 structure. The CMP binding site is located in the deep cleft between the two Rossmann domains. Nevertheless, the CMP only forms interactions with residues in the C-terminal domain. The binding of CMP to the protein causes a large closure movement of the N-terminal Rossmann domain toward the C-terminal nucleotide-binding domain. Ser 143 of the N-terminal domain moves up to hydrogen-bond to Tyr 388 of the C-terminal domain. Both Ser 143 and Tyr 388 form hydrogen bonds to a water molecule, which in turn hydrogen-bonds to the terminal phosphate oxygen of CMP. These interactions may trigger the closure between the two domains. Additionally, a short helix near the active site seen in the apo structure becomes disordered upon binding to CMP. This helix may swing down upon binding to donor CMP-sialic acid to form the binding pocket for an acceptor.

Crystallization↗

Stressing the group: social identity and the unfolding dynamics of responses to stress.

Participants in the British Broadcasting Corporation (BBC) prison study were randomly assigned to high-status (guard) and low-status (prisoner) groups. Structural interventions increased the prisoners' sense of shared group identity and their willingness to challenge the power of the guards. Psychometric, physiological, behavioral, and observational data support the hypothesis that identity-based processes also affected participants' experience of stress. As prisoners' sense of shared identity increased, they provided each other with more social support and effectively resisted the adverse effects of situational stressors. As guards' sense of shared identity declined, they provided each other with less support and succumbed to stressors. Findings support an integrated social identity model of stress that addresses intragroup and intergroup dynamics of the stress process.

Adult↗

Understanding the psychosocial needs of HIV-positive women: a qualitative study.

The purpose of this study was to engage women with HIV disease in a qualitative needs assessment for psychological services. Focus groups/interviews were held to develop an understanding of these women's experiences and perceptions of services needed within a support group format. Results support women's interest in and perceived need for psychosocial group intervention and provide feedback on how to structure groups, including considerations for the facilitator, concrete barriers to address, and attention to group attributes and guidelines. These results support ongoing development of psychosocial support groups for women with HIV disease and further exploration of the efficacy of group models for the diverse subgroups of women with HIV/AIDS.

Acquired Immunodeficiency Syndrome↗

[The effect of a value clarification program on value clarification in juvenile delinquents].

PURPOSE: The purpose of this study was to identify the effects of a value clarification program on value clarification in juvenile delinquents. This study employed a two-group pre-post test study design. Data was collected from 16 subjects from Sept. 29 to Dec. 26, 2003 at N middle school in Seoul, Korea. 9 subjects constituted the control, while the experimental group was composed of 7 subjects. METHOD: The structured group therapy used in this study was developed on the basis of Raths et al. (1978) theory. The subjects participated in 10 sessions of therapy that lasted 60 minutes. The instruments used were value clarification Test (Lee, 1988), and SPSS Window. RESULT: The experimental group showed a significant increase in value clarification after their participation in the program. CONCLUSION: Based upon the findings it was concluded that a value clarification program was effective in improving value clarification in juvenile delinquents in the study.

Adolescent↗

A randomized trial of a lay person-led self-management group intervention for back pain patients in primary care.

STUDY DESIGN: Randomized, controlled trial. OBJECTIVE: To evaluate a four-session self-management group intervention for patients with pain in primary care, led by trained lay persons with back pain. The intervention was designed to reduce patient worries, encourage self-care, and reduce activity limitations. BACKGROUND DATA: Randomized trials of educational interventions suggest that activating interventions may improve back pain outcomes. Expert opinion increasingly regards effective self-management of back pain as important in achieving good outcomes. In this study, an educational intervention designed to activate patients and support effective self-management was evaluated. METHODS: Six to 8 weeks after a primary care visit for back pain, patients were invited to participate in an educational program to improve back pain self-management. Those showing interest by returning a brief questionnaire became eligible for the study. Participants (n = 255) randomly were assigned to either a self-management group intervention or to a usual care control group. The effect of the intervention, relative to usual care, was assessed 3, 6, and 12 months after randomization, controlling for baseline values. The intervention consisted of a four-session group applying problem-solving techniques to back pain self-management, supplemented by educational materials (book and videos) supporting active management of back pain. The groups were led by lay persons trained to implement a fully structured group protocol. The control group received usual care, supplemented by a book on back pain care. RESULTS: Participants randomly assigned to the self-management groups reported significantly less worry about back pain and expressed more confidence in self-care. Roland Disability Questionnaire Scores were significantly lower among participants in the self-management groups relative to the usual care controls at 6 months (P = 0.007), and this difference was sustained at 12 months at borderline significance levels (P = 0.09). Among self-management group participants, 48% showed a 50% or greater reduction in Roland Disability Questionnaire Score at 6 months, compared with 33% among the usual care controls. CONCLUSIONS: Self-management groups led by trained lay persons following a structured protocol were more effective than usual care in reducing worries, producing positive attitudes toward self-care, and reducing activity limitations among patients with back pain in primary care.

Activities of Daily Living↗

Effects of chemically defined structured lipid emulsions on reticuloendothelial system function and morphology of liver and lung in a continuous low-dose endotoxin rat model.

BACKGROUND: This study was undertaken to determine the effect of chemically defined structured lipids on nonspecific host defense and on histologic patterns of liver and lungs compared with a physical mixture of long-chain triglycerides and medium-chain triglycerides in a continuous low-dose endotoxin rat model. METHODS: Forty male Sprague-Dawley rats, divided into four feeding groups (structured lipids, structured lipids+endotoxin, physical mixture, physical mixture+endotoxin), received total parenteral nutrition for 48 hours. During the first part of the study, 24 animals were given an injection of live Escherichia coli labeled with radioactive iron (59Fe) to investigate the function of the reticuloendothelial system. During the second part of the study, the liver and lungs of 16 animals were histologically examined using light and electron microscopy. RESULTS: Despite the similar values in the control groups, the animals receiving structured lipids+endotoxin sequestered a significantly greater percentage of bacteria in the liver and spleen (p < or = .01) and a significantly lesser percentage in the lung (p < or = .05) compared with the animals given physical mixture+endotoxin as part of their diet. Moreover, rats in the physical mixture+endotoxin group showed a microscopically evaluated higher fatty infiltration in the liver than did the structured lipids+endotoxin group. CONCLUSIONS: The results of this study indicate that chemically defined structured lipids reduce fatty infiltration of the liver compared with a physical mixture of the same compounds in an animal model of metabolic stress. They were accompanied by a better function of the reticuloendothelial system and a lesser bacterial sequestration in the lungs.

Animals↗

Assigning genomic sequences to CATH.

We report the latest release (version 1.6) of the CATH protein domains database (http://www.biochem.ucl. ac.uk/bsm/cath ). This is a hierarchical classification of 18 577 domains into evolutionary families and structural groupings. We have identified 1028 homo-logous superfamilies in which the proteins have both structural, and sequence or functional similarity. These can be further clustered into 672 fold groups and 35 distinct architectures. Recent developments of the database include the generation of 3D templates for recognising structural relatives in each fold group, which has led to significant improvements in the speed and accuracy of updating the database and also means that less manual validation is required. We also report the establishment of the CATH-PFDB (Protein Family Database), which associates 1D sequences with the 3D homologous superfamilies. Sequences showing identifiable homology to entries in CATH have been extracted from GenBank using PSI-BLAST. A CATH-PSIBLAST server has been established, which allows you to scan a new sequence against the database. The CATH Dictionary of Homologous Superfamilies (DHS), which contains validated multiple structural alignments annotated with consensus functional information for evolutionary protein superfamilies, has been updated to include annotations associated with sequence relatives identified in GenBank. The DHS is a powerful tool for considering the variation of functional properties within a given CATH superfamily and in deciding what functional properties may be reliably inherited by a newly identified relative.

Amino Acid Sequence↗

Crystal structures of bovine beta-lactoglobulin in the orthorhombic space group C222(1). Structural differences between genetic variants A and B and features of the Tanford transition.

The crystal structures of beta-lactoglobulin genetic variants A and B have been determined in the orthorhombic space group C222(1) (lattice Y) by X-ray diffraction at 2.0 A and 1.95 A resolution, respectively. The structural comparison shows that both variants exhibit the open conformation of the EF loop at the pH of crystallization (pH 7.9), in contrast to what has been reported for the same genetic variants at pH 7.1 in the trigonal space group P3221 (lattice Z) [Qin, B.Y., Bewley, M.C., Creamer, L.K., Baker, E.N. & Jameson, G.B. (1999) Protein Sci. 8, 75-83]. Furthermore, it was found that the stereochemical environment of Tyr42 changes significantly with pH variation between pH 7 and pH 8. This may provide a structural explanation for an as yet unexplained feature of the Tanford transition, namely the increase in exposure of a tyrosine residue.

Animals↗

[Percutaneous mitral commissurotomy: simplified new method].

We report a new simplified method of mitral dilatation done on 146 patients. This technique use the Inoue balloon with progressive diameters under ultrasonographic control, avoiding the arterial part of the dilatation. The population include 9 pregnant women, 13 children, 13 with restenosis and closed heart and 12 restenosis after dilatation. Mean age is 32 +/- 16 years (9 to 72) and sex ratio 3.7 (114 F/32 M). Three groups are individualized according to histopathologic exam of mitral structure, group I (26%) concern good indication and III (32%) bad indication for this technique, group II (42%) contain intermediate indications. Commissurotomy increase the mean mitral square for 0.2 to 1.9 +/- 0.1 cm_. We observe 3 cases of chirurgical mitral insufficiency needing remplacement recruited for 2 patients from the group III. Mean fluoroscopic exposition time is 5.2 +/- 3.3 mn and procedure duration 18 +/- 11 mn. Hospitalisation duration is one day for 95% of the patients. This method remaining simple, efficient and safe permit a gain in time of 70% with a good comfort for patient and a return to work on the 4th day.

Adolescent↗

Racial bias in the assessment of cognitive functioning of older adults.

This study was undertaken to determine if the difference in assessed cognition between Black/African-American and White older adults was due differential item functioning (DIF) and/or differences in the effect of background variables. Participants were 15257 adults aged 50 and older surveyed in the Study of Asset and Health Dynamics of the Oldest Old (AHEAD) and Health and Retirement Study (HRS). The cognitive measure was a modified telephone interview for cognitive status. The analytic strategy was a multiple group structural equation model grounded in item response theory. Results suggest that most (89%) of the group difference could be attributed to measurement or structural differences, the remainder being not significantly different from zero (p=0.193). Most items displayed racial DIF, accounting for most of the group difference. After controlling for DIF, the group difference that remained could be attributed to heterogeneity in the effect of background variables. For example, low education was more deleterious for Black/African-Americans, and high income conferred an advantage only for Whites. These findings underscore the importance of efforts to generate culture-fair measurement devices. However, culture-fair assessments may attenuate, but not eliminate, group differences in assessed cognition due to the incommensurate action of background variables

Black or African American↗

The guanidino-group modifying enzymes: structural basis for their diversity and commonality.

The guanidino-group modifying enzyme (GME) superfamily contains many drug targets, including metabolic enzymes from pathogenic microorganisms as well as key regulatory proteins from higher eukaryotes. These enzymes, despite their diverse sequences, adopt the common alpha/beta propeller fold and catalyze the modification of (methylated) guanidino groups. Our structural superposition and structure-based alignment for the GMEs have identified key residues that are involved in the catalysis and substrate binding. We have shown that conserved guanidino-carboxyl interactions are utilized in two different ways; the acidic residues in the catalytic site form hydrogen bonds to the substrate guanidino group, and the enzyme Arg residues at several key positions recognize the carboxyl group of the substrate and fix its orientation. Based on this observation, we have proposed rules for classifying the GME sequences and predicting their molecular function from the conservation of the key acidic and Arg residues. Other novel motifs have been identified, which involve residues that are not in direct contact with the substrate but are likely to stabilize the active-site conformation through hydrogen-bonding networks. In addition, we have examined the domain architecture of the GMEs. Although most members consist of a single catalytic domain, fold recognition analysis has identified a likely bifunctional enzyme from a cyanobacterium. It has also revealed common immunoglobulin-like beta-sandwich domains found in the enzymes that recognize protein substrates. These findings will be useful for predicting the precise mechanism of action for potential novel targets and designing therapeutic compounds against them.

Amidinotransferases↗

Latarcins, antimicrobial and cytolytic peptides from the venom of the spider Lachesana tarabaevi (Zodariidae) that exemplify biomolecular diversity.

Seven novel short linear antimicrobial and cytolytic peptides named latarcins were purified from the venom of the spider Lachesana tarabaevi. These peptides were found to produce lytic effects on cells of diverse origin (Gram-positive and Gram-negative bacteria, erythrocytes, and yeast) at micromolar concentrations. In addition, five novel peptides that share considerable structural similarity with the purified latarcins were predicted from the L. tarabaevi venom gland expressed sequence tag data base. Latarcins were shown to adopt amphipathic alpha-helical structure in membrane-mimicking environment by CD spectroscopy. Planar lipid bilayer studies indicated that the general mode of action was scaled membrane destabilization at the physiological membrane potential consistent with the "carpet-like" model. Latarcins represent seven new structural groups of lytic peptides and share little homology with other known peptide sequences. For every latarcin, a precursor protein sequence was identified. On the basis of structural features, latarcin precursors were split into three groups: simple precursors with a conventional prepropeptide structure; binary precursors with a typical modular organization; and complex precursors, which were suggested to be cleaved into mature chains of two different types.

Amino Acid Sequence↗

[A1 and A2 blood group substances: are there structural differences?].

Blood group substances were extracted from erythrocytes of blood groups A1 and A2 and separated using HPTLC. Identification of blood group A was carried out on the chromatogramm using the PAP-technique. The specific demonstration of the serologically active glycosphingolipids allowed a comparison of the A1 and A2 blood group substance bands. The difference between the A1 and A2 Substances appears to be only a quantitative one.

ABO Blood-Group System↗

Single patient (n-of-1) trials with binary treatment preference.

The use of a fully parametric Bayesian method for analysing single patient trials based on the notion of treatment 'preference' is described. This Bayesian hierarchical modelling approach allows for full parameter uncertainty, use of prior information and the modelling of individual and patient sub-group structures. It provides updated probabilistic results for individual patients, and groups of patients with the same medical condition, as they are sequentially enrolled into individualized trials using the same medication alternatives. Two clinically interpretable criteria for determining a patient's response are detailed and illustrated using data from a previously published paper under two different prior information scenarios.

Amitriptyline↗

Group psychotherapy in an acute inpatient setting.

The literature on inpatient group psychotherapy reveals an emphasis on here-and-now structured group activity as opposed to in-depth psychodynamic work. Historical material is rarely accessed and therapeutic strategies are focused on interpersonal work within the group. In this paper, groups currently operating in an acute psychiatric setting are described, and problems and practicalities in establishing inpatient groups are discussed.

Acute Disease↗

The nominal group technique: a research tool for general practice?

Qualitative methods are increasingly recognized as valuable, yet practitioners face difficult decisions in their choice of method and the process of analysis. The nominal group technique combines quantitative and qualitative data collection in a group setting, and avoids problems of group dynamics associated with other group methods such as brainstorming, Delphi and focus groups. Idea generation and problem solving are combined in a structured group process, which encourages and enhances the participation of group members. The stages involved in conducting a nominal group are described, and practical problems of its use in a health care setting are discussed with reference to a study of the priorities of care of diabetic patients, carers and health professionals. Some potential applications of the technique in audit and exploratory research are also outlined.

Data Collection↗